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Nat Commun. 2017 Jan 27;8:14147. doi: 10.1038/ncomms14147.

A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes.

Shu L1,2, Hoo RL1,2, Wu X1,2, Pan Y1,2, Lee IP1,2, Cheong LY1,3, Bornstein SR4, Rong X5, Guo J5, Xu A1,2,3.

Author information

1
State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
2
Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
3
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
4
Department of Medicine, University of Dresden, 01307 Dresden, Germany.
5
Joint Laboratory of Guangdong and Hong Kong on Metabolic Diseases, Guangdong Pharmaceutical University, 510000 Guangzhou, China.

Abstract

The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor α, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis.

PMID:
28128199
PMCID:
PMC5290165
DOI:
10.1038/ncomms14147
[Indexed for MEDLINE]
Free PMC Article

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